Reduction of the aortic inflammatory response in spontaneous atherosclerosis by blockade of macrophage migration inhibitory factor (MIF)

Burger‐Kentischer, Anke; Göbel, Heike; Kleemann, Robert; Zernecke, Alma; Bucala, Richard; Leng, Lin; Finkelmeier, Doris; Geiger, G.; Schaefer, Hans E.; Schober, Andreas; Weber, Christian; Brunner, Herwig; Rütten, Hartmut; Ihling, Christian

doi:10.1016/j.atherosclerosis.2005.03.028

Cited by 110 publications

(89 citation statements)

References 36 publications

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“…Although the data from the present study support an indirect pathway whereby MIF induces release of secondary mediators such as CCL2, it is also possible that MIF may be expressed on the endothelial surface and induce monocyte recruitment via a direct pathway. Indeed, the mechanisms at work in the microvasculature, as assessed in the present study, may be distinct from those active in large atheromatous arteries where MIF expression in endothelial cells is markedly elevated (28,29). Together, these findings suggest that MIF can induce monocyte recruitment via multiple mechanisms.…”

Section: Discussionmentioning

confidence: 54%

“…Despite this, results of some studies have raised the possibility that MIF may promote macrophage recruitment specifically. In models of atherogenesis, MIF blockade has been shown to inhibit intimal accumulation of CD68 ϩ monocytes (28,29). It is well-established that monocytes are the major leukocyte subgroup recruited to the vascular wall in these models.…”

Section: Discussionmentioning

confidence: 99%

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Macrophage Migration Inhibitory Factor Induces Macrophage Recruitment via CC Chemokine Ligand 2

Gregory

Morand

McKeown

et al. 2006

The Journal of Immunology

172

155

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Macrophage migration inhibitory factor (MIF) was originally identified for its ability to inhibit the random migration of macrophages in vitro. MIF is now recognized as an important mediator in a range of inflammatory disorders. We recently observed that the absence of MIF is associated with a reduction in leukocyte-endothelial cell interactions induced by a range of inflammatory mediators, suggesting that one mechanism whereby MIF acts during inflammatory responses is by promoting leukocyte recruitment. However, it is unknown whether MIF is capable of inducing leukocyte recruitment independently of additional inflammatory stimuli. In this study, we report that MIF is capable of inducing leukocyte adhesion and transmigration in postcapillary venules in vivo. Moreover, leukocytes recruited in response to MIF were predominantly CD68+ cells of the monocyte/macrophage lineage. Abs against the monocyte-selective chemokine CCL2 (JE/MCP-1) and its receptor CCR2, but not CCL3 and CXCL2, significantly inhibited MIF-induced monocyte adhesion and transmigration. CCL2−/− mice displayed a similar reduction in MIF-induced recruitment indicating a critical role of CCL2 in the MIF-induced response. This hypothesis was supported by findings that MIF induced CCL2 release from primary microvascular endothelial cells. These data demonstrate a previously unrecognized function of this pleiotropic cytokine: induction of monocyte migration into tissues. This function may be critical to the ability of MIF to promote diseases such as atherosclerosis and rheumatoid arthritis, in which macrophages are key participants.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Induces Macrophage Recruitment via CC Chemokine Ligand 2

Gregory

Morand

McKeown

et al. 2006

The Journal of Immunology

172

155

View full text Add to dashboard Cite

show abstract

“…A recent publication showed that treatment with anti-MIF antibody led to the reduction of a variety of inflammatory mediators typically associated with atherosclerosis, including circulating levels of fibrinogen and IL-6 together with the reduction of local aortic expression of ICAM-1 in apolipoprotein E-deficient mice 22) . Lin et al previously showed that MIF stimulates ICAM-1 expression in endothelial cells 6) .…”

Section: Discussionmentioning

confidence: 99%

The Potential Role of Macrophage Migration Inhibitory Factor on the Migration of Vascular Smooth Muscle Cells

Okamoto

Atsumi

Shimizu

et al. 2008

JAT

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“…MIF expression within plaques is likely to promote neovascularization because MIF has been shown to mediate proliferation of cultured endothelial cells (31). Treatment of a strain of mice, which spontaneously develop atherosclerotic lesions (apolipoprotein E-deficient mice) with neutralizing anti-MIF Ab, led to a reduction of a variety of inflammatory mediators typically associated with atherosclerosis (32), implying that MIF may also play an important role in arterial intima inflammation. A number of cytokines and enzymes known to be induced by hypoxia are expressed by foam cells in human atherosclerotic plaques, including VEGF (33), platelet-derived growth factor (PDGF) (34), TNF-␣, IL-1 (35), CCL2 (36), MMP-1 and -7 (37,38).…”

Section: Atherosclerosismentioning

confidence: 99%

Hypoxia Regulates Macrophage Functions in Inflammation

Murdoch

Muthana

Lewis

2005

The Journal of Immunology

417

329

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The presence of areas of hypoxia is a prominent feature of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of joints with rheumatoid arthritis, healing wounds, and sites of bacterial infection. These areas form when the blood supply is occluded and/or unable to keep pace with the growth and/or infiltration of inflammatory cells in a given area. Macrophages are present in all tissues of the body where they normally assist in guarding against invading pathogens and regulate normal cell turnover and tissue remodeling. However, they are also known to accumulate in large numbers in such ischemic/hypoxic sites. Recent studies show that macrophages then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. In the present study, we outline and compare the phenotypic responses of macrophages to hypoxia in different diseased states and the implications of these for their progression and treatment.

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Reduction of the aortic inflammatory response in spontaneous atherosclerosis by blockade of macrophage migration inhibitory factor (MIF)

Cited by 110 publications

References 36 publications

Macrophage Migration Inhibitory Factor Induces Macrophage Recruitment via CC Chemokine Ligand 2

Macrophage Migration Inhibitory Factor Induces Macrophage Recruitment via CC Chemokine Ligand 2

The Potential Role of Macrophage Migration Inhibitory Factor on the Migration of Vascular Smooth Muscle Cells

Hypoxia Regulates Macrophage Functions in Inflammation

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